AB1094 GUSELKUMAB EFFECT ON INFLAMMATORY CARDIOVASCULAR (CV) RISK BIOMARKERS, EFFICACY, AND SAFETY IN PSORIATIC ARTHRITIS PATIENTS WITH CV RISK FACTORS: POST-HOC ANALYSIS OF 2 PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDIES
Authors: A. Kavanaugh, E. Soriano, J. Dutz, C. Selmi, J. Yu, E. Rampakakis, M. Shawi, A. M. Bravo Perdomo, F. Lavie, L. Coates
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> PsA has been associated with an increased risk of cardiovascular disease (CVD), likely due to accelerated atherosclerosis secondary to chronic inflammation.<sup>[1]</sup> The number of CV risk factors has been shown to correlate with PsA disease activity (DA).<sup>[2]</sup> <h3>Objectives</h3> Describe effect of guselkumab (GUS) on inflammatory biomarkers that predict CVD, and its efficacy and safety, in patients (pts) with active PsA and concurrent CV risk factors. <h3>Methods</h3> DISCOVER (D)1&amp;2 enrolled adults with active PsA despite standard therapies. D1 pts (31% received 1-2 prior TNF inhibitors [i]), had tender and swollen joint counts (TJC/SJC) each ≥3 and CRP ≥0.3 mg/dL; D2 pts (biologic-naïve) had TJC/SJC each ≥5 and CRP ≥0.6 mg/dL. Pts were randomized 1:1:1 to GUS 100 mg every 4 weeks (Q4W); GUS 100 mg at W0, W4, then Q8W; or placebo (PBO)→GUS 100 mg Q4W at W24. Pts included in this analysis had ≥1 of the following CV risk factors: obesity; smoking (past or current); or history of hypertension, diabetes mellitus (DM), or hyperlipidemia. Changes in high-sensitivity (hs) CRP and neutrophil–lymphocyte ratio (NLR) were compared between GUS vs PBO with mixed models adjusting for baseline (BL) levels. Achievement of endpoints at W24 (missing data imputed as no response) was compared in GUS vs PBO with logistic regression adjusting for BL levels, prior TNFi use, and BL DMARD use: American College of Rheumatology (ACR) response criteria, Investigator's Global Assessment (IGA) of psoriasis score 0/1, DA Index for PsA (DAPSA) low DA (LDA)/remission, PsA DA Score (PASDAS) LDA, minimal DA (MDA), Psoriasis Area and Severity Index (PASI) responses, Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) response, Health Assessment Questionnaire Disability Index (HAQ-DI) response, and enthesitis and dactylitis resolution. The incidence of major adverse CV events (MACE; cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) was assessed through W100. <h3>Results</h3> Of 1120 enrolled pts, 758 had ≥1 CV risk factor (259 Q4W, 252 Q8W, 247 PBO); of these, 448 (59%) were obese, 420 (55%) had hypertension, 315 (42%) were smokers, 171 (23%) had hyperlipidemia, and 103 (14%) had DM. Through W24, GUS significantly reduced hsCRP and NLR vs PBO (Figure 1). Response rates at W24 were significantly higher with GUS vs PBO for all assessed endpoints (Table 1). During the PBO-controlled period, one pt each had a MACE in the PBO (0.9 [95% CI: 0.0-4.9]/100 person-years [PY]) and pooled GUS (0.4; 0.0-2.4)/100PY groups. In the pooled GUS group, the incidence (95% CI) of MACE was 0.2 (0.0-0.8)/100PY over 1 year and 0.3 (0.1-1.0)/100PY over 2 years. <h3>Conclusion</h3> In the subgroup of PsA pts with concurrent CV risk factors, GUS was associated with significant reductions in hsCRP and NLR and significantly higher response rates vs PBO for all PsA domains assessed. MACE incidence was similar to that in the overall D1/D2 population.<sup>[3]</sup> These findings support the efficacy of GUS on systemic inflammation and its cardiovascular safety. <h3>References</h3> [1]Zheng Z, et al. <i>Front Cardiovasc Med</i>. 2022;9:835439 [2]Ferraz-Amaro I, et al. <i>Medicina (Kaunas</i>). 2020;56:415 [3]Rahman P, et al. <i>Arthritis Rheumatol.</i> 2021;73 (suppl 9) <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> Arthur Kavanaugh Consultant of: AbbVie, Amgen, BMS, Janssen, Eli Lilly, Novartis, Pfizer and UCB, Enrique Soriano Speakers bureau: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Janssen, Novartis, Roche, and UCB, Consultant of: AbbVie, Janssen, Novartis, and Roche, Grant/research support from: AbbVie, Janssen, Novartis, Pfizer, Roche, and UCB, Jan Dutz Shareholder of: Solius, Speakers bureau: AbbVie, Amgen, Bausch, Eli Lilly, Leo, Janssen, Novartis, Sanofi and Pfizer, Consultant of: Bristol Myers Squib, Grant/research support from: Corbus, Eli Lilly, Carlo Selmi Speakers bureau: AbbVie, Amgen, Alfa-Wassermann, Biogen, Eli-Lilly, Galapagos, Janssen, Novartis, SOBI, Consultant of: AbbVie, Amgen, Alfa-Wassermann, Biogen, Eli-Lilly, Galapagos, Janssen, Novartis, SOBI, Grant/research support from: AbbVie, Amgen, Pfizer, Jenny Yu Shareholder of: Johnson &amp; Johnson, Employee of: Janssen Research &amp; Development, LLC, Janssen Pharmaceutical Companies of Johnson &amp; Johnson, Emmanouil Rampakakis Consultant of: Janssen, Employee of: JSS Medical Research, Inc., May Shawi Shareholder of: Johnson &amp; Johnson, Employee of: Immunology Global Medical Affairs, Janssen Pharmaceutical Companies of Johnson &amp; Johnson, Ana Maria Bravo Perdomo Shareholder of: Johnson &amp; Johnson, Employee of: Immunology Global Medical Affairs, Janssen Latin America, Frederic Lavie Shareholder of: Johnson &amp; Johnson, Employee of: Immunology Global Medical Affairs, Janssen Pharmaceutical Companies of Johnson &amp; Johnson, Laura Coates Speakers bureau: AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Medac, Novartis, Pfizer and UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Gilead, Galapagos, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, and UCB.